Microstructural properties within the amygdala and affiliated white matter tracts across adolescence

Abstract

The amygdala is a heterogenous set of nuclei with widespread cortical connections that continues to develop postnatally with vital implications for emotional regulation. Using high-resolution anatomical and multi-shell diffusion MRI in conjunction with novel amygdala segmentation, cutting-edge tractography, and Neurite Orientation Dispersion and Density (NODDI) methods, the goal of the current study was to characterize age associations with microstructural properties of amygdala subnuclei and amygdala-related white matter connections across adolescence ( N = 61, 26 males; ages of 8–22 years). We found age-related increases in the Neurite Density Index (NDI) in the lateral nucleus (LA), dorsal and intermediate divisions of the basolateral nucleus (BLDI), and ventral division of the basolateral nucleus and paralaminar nucleus (BLVPL). Additionally, there were age-related increases in the NDI of the anterior commissure, ventral amygdalofugal pathway, cingulum, and uncinate fasciculus, with the strongest age associations in the frontal and temporal regions of these white matter tracts. This is the first study to utilize NODDI to show neurite density of basolateral amygdala subnuclei to relate to age across adolescence. Moreover, age-related differences were also notable in white matter microstructural properties along the anterior commissure and ventral amydalofugal tracts, suggesting increased bilateral amygdalae to diencephalon structural connectivity. As these basolateral regions and the ventral amygdalofugal pathways have been involved in associative emotional conditioning, future research is needed to determine if age-related and/or individual differences in the development of these microstructural properties link to socio-emotional functioning and/or risk for psychopathology.

Immature excitatory neurons in the amygdala come of age during puberty

“…Increases in the total numbers of neurons in neighboring nuclei might still occur, but as the result of displacement of PL neurons through non-migratory means like the growth of other nearby cells. This is consistent with increases in neurite density (including axons and dendrites) measured between 8 and 22 years old in the human BLVPL discussed in Section 3.2 ( Azad et al, 2021 ). Additionally, the number of oligodendrocytes also increases throughout the amygdala in macaques, which may also account for volumetric increases in individual subnuclei ( Chareyron et al, 2012 ).…”

“…The volume of the BLVPL decreased in boys, but remained unchanged in girls, a change that was more strongly associated with chronological age than pubertal stage ( Campbell et al, 2021 ). The same segmentation of BLVPL also shows that the density of neurites (axons and dendrites) increases in this region between 8 and 22 years of age in both boys and girls ( Azad et al, 2021 ). It is presently unknown how decreased volume alongside increased density of neuropil relate to the changes in cellular density and neuronal maturation in the PL, and the implications of these findings for sex-specific development of the PL.…”

“…Activity into and within the PL may influence the developmental trajectory of late-maturing neurons. Interestingly, white matter tracts associated with the amygdala including the uncinate fasciculus and the cingulum show increased neurite density and mature connectivity patterns during puberty ( Azad, 2021 , Jalbrzikowski et al, 2017 ). If these axonal projections with protracted development make contacts within the PL, their delayed inputs could result in late maturation of activity-dependent aspects of PL neuron growth.…”

“…As discussed in Section 2.1 , there is a white matter tract along the ventral border of the PL with fibers that appear to innervate the MPL and LPL islands ( Sorrells et al, 2019 ). This white matter tract may include axons from the uncinate fasciculus, which increases in neurite density between 8 and 22 years of age ( Azad et al, 2021 ). Other white matter tracts that connect with the amygdala also increased in neurite density during these ages, including the cingulum, the ventral amygdalofugal pathway, and the anterior commissure; these changes did not differ by sex ( Azad et al, 2021 ).…”

Childhood Threat Is Associated With Lower Resting-State Connectivity Within a Central Visceral Network

“…Thus, the amygdalofugal pathway may be a promising candidate neural mechanism underlying the relationship between childhood threat and amygdala-sgACC connectivity found here. Further, a recent study showed greater neurite density within the ventral amygdalofugal pathway with age, perhaps indicating greater fiber packing density and/or myelination of the tract ( Azad et al, 2021 ). Future work will be needed to examine childhood adversity-related microstructural differences within this pathway across development and to determine its multimodal relationship to functional connectivity among these ROIs.…”